Herpesvirus sylvilagus infection of cottontail rabbits results in a lymphoproliferative disease characterized by leukocytosis, splenomegaly, apparent T-cell proliferation, and the presence of permissively infected lymphocytes. In addition, viral genomes can be detected in lymphocytes in a circular form. This virus reportedly induces a lymphoma in the cottontail rabbit which is the only known host for this agent. We intend to study the virological and immunological events during H. sylvilagus infection in the cottontail rabbit. Using virus molecular probes, we will examine the virus-lymphocyte relationship including: (1) the use of H. sylvilagus molecular probes for detection of viral genomes (2) identification of lymphocytes permissively and latently infected during the course of infection (3) In vitro infection and transformation of lymphoid cells by H. sylvilagus (4) identification and characterization of the lymphoproliferative disorder which occurs following infection with H. sylvilagus. Immunological studies will include: (1) development of H. sylvilagus specific humoral antibodies (2) B cell activation (3) non-specific cytotoxic activity (4) major histocompatibility virus restricted cytotoxic T cell responses. These studies should provide useful information about the early events of a lymphotropic herpesvirus infection. The role of latent viral genome in disease manifestation and the immunological mechanisms responsible for host recovery will be investigated. These studies will determine if H. sylvilagus infection is an appropriate model for human lymphotropic herpes virus induced diseases. Such a model will be important for future investigation of immune mechanisms and antiviral chemotherapy as a means to control herpesvirus induced lymphoproliferative disease.